Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Pharmacy, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China; Department of Pharmacy, Hubei Province Academy of Traditional Chinese Medicine, Wuhan 430074, China.
Biomed Pharmacother. 2019 Jan;109:2396-2408. doi: 10.1016/j.biopha.2018.11.087. Epub 2018 Nov 30.
OBJECTIVE: Compound sophorae decoction, a Chinese medicinal formulae composed of six Chinese herbs, is effective for the clinical treatment of ulcerative colitis (UC). Some of its effective monomers had been proven to have suppressive effect on UC models. The aim of this study is to further explore the mechanism whether compound sophorae decoction ameliorates dextran sodium sulfate (DSS)-induced mice colitis by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells. METHODS: Experimental model of UC, established by drinking water with DSS, was treated with compound sophorae decoction and mesalazine. The stool, activity, body weight of the mice, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The expression of phosphorylated nuclear factor-kappaB (NF-κB) p65, STAT3 and phosphorylated STAT3 in colonic tissues were determined by western blotting and immunohistochemistry. The percentage of Th17 and Treg cells in spleen and mesenteric lymph nodes (MLNs) were detected by flow cytometry. The levels of transcription factor ROR-γt and FOXP3 in colon tissues were detected by qRT-PCR and immunohistochemistry. RESULTS: The aqueous extract of compound sophorae decoction was able to improve the symptoms and pathological damage of mice. The body weight of mice were increased and DAI were significantly decreased; ulcers were slighter than DSS group. The administration of compound sophorae decoction reduced the level of inflammatory factors interleukin (IL)-1β, tumor necrosis factor (TNF)-α and phospho-NF-κB p65, and also decreased the proportions of Th17 cells in spleen and MLNs and the expression of ROR-γt, IL-17A, STAT3, IL-6 in colonic tissues; while the percentage of Treg cells in spleen and MLNs and the expression of FOXP3, transforming growth factor (TGF)-β1, IL-10 in colonic tissues were upregulated. CONCLUSION: Overall, this study suggested that compound sophorae decoction significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.
目的：复方苦参汤是由 6 种中草药组成的中药方剂，对溃疡性结肠炎（UC）的临床治疗有效。其一些有效单体已被证明对 UC 模型具有抑制作用。本研究旨在进一步探讨复方苦参汤通过调节辅助性 T 细胞 17（Th17）与调节性 T（Treg）细胞平衡来改善葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的机制。
方法：采用饮用含 DSS 的水建立 UC 实验模型，并用复方苦参汤和美沙拉嗪进行治疗。观察粪便、活动、小鼠体重、结肠长度和结肠组织病理学，以评估结肠炎的严重程度。采用 ELISA 检测结肠组织中细胞因子的浓度。采用 Western blot 和免疫组化检测结肠组织中磷酸化核因子-κB（NF-κB）p65、STAT3 和磷酸化 STAT3 的表达。采用流式细胞术检测脾和肠系膜淋巴结（MLN）中 Th17 和 Treg 细胞的百分比。采用 qRT-PCR 和免疫组化检测结肠组织中转录因子 ROR-γt 和 FOXP3 的水平。
结果：复方苦参汤的水提取物能够改善小鼠的症状和病理损伤。小鼠体重增加，DAI 显著降低；溃疡较 DSS 组减轻。复方苦参汤治疗降低了炎症因子白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和磷酸化 NF-κB p65 的水平，也降低了脾和 MLN 中 Th17 细胞的比例以及结肠组织中 ROR-γt、IL-17A、STAT3、IL-6 的表达；而脾和 MLN 中 Treg 细胞的比例以及结肠组织中 FOXP3、转化生长因子（TGF）-β1、IL-10 的表达上调。
结论：总之，本研究表明，复方苦参汤可显著改善 DSS 诱导的结肠炎小鼠的症状和病理损伤，并通过调节 Th17/Treg 细胞平衡影响免疫功能。
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